spirolactones

Spirolactones are a class of organic compounds in which a cyclic ester (lactone) forms part of a spirocyclic system, sharing a single atom between two rings. The spiro atom is typically a quaternary carbon that is part of both rings, and the lactone carbonyl is incorporated into the ester moiety. This arrangement creates a rigid, three-dimensional framework with two rings oriented orthogonally to one another.

Structural features: The lactone ring can range from five to seven members, and the second ring can be a cycloalkane, an aryl group, or another heterocycle. The defining characteristic is the spiro connection at one atom, which makes the molecule inherently chiral in many cases and often confers restricted conformational flexibility.

Synthesis: Spirolactones are usually fabricated by intramolecular lactonization of hydroxy acids, where a hydroxyl group is positioned to attack a nearby carboxylic acid or activated derivative. Alternative approaches include spirocyclization strategies that link a preformed ring system to a hydroxy or carboxy precursor, or methods such as ring-closing metathesis to form the second ring around a growing lactone framework.

Properties and applications: The rigid spiro center provides well-defined three-dimensional shapes, making spirolactones valuable as chiral building blocks in organic synthesis and medicinal chemistry. They appear in synthetic libraries and in various natural product families, where the motif can influence biological activity and receptor interactions. Due to their modularity, spirolactones are used to construct more complex spirocyclic architectures and to explore structure–activity relationships in drug discovery.

See also: lactone, spiro compound, spirocycle.